JPC SYSTEMIC PATHOLOGY
Signalment (JPC 2641247): 9-year‑old male chow chow dog
HISTORY: This dog had a one month history of weight loss. Three days prior to euthanasia, the dog developed episodic blindness, pacing, head pressing, seizures, lethargy, and high fever (106°F).
HISTOPATHOLOGIC DESCRIPTION: Cerebrum, level of the hippocampus: Multifocally, most severely affecting periventricular, cerebral, choroidal, and meningeal blood vessels, there is fibrinonecrotic vasculitis with discontinuity of the endothelium, disruption of the tunica intima and tunica media, and expansion of the adventitia and/or Virchow-Robin space by numerous viable and degenerate neutrophils, macrophages, and lymphocytes, with fewer plasma cells admixed with eosinophilic cellular and karyorrhectic debris (necrosis), abundant eosinophilic beaded to fibrillar material (fibrin), and rare hemorrhage. Some vessel walls are completely replaced by fibrin. Inflammatory cells multifocally infiltrate the surrounding leptomeninges, choroid plexus and neuropil. Occasionally, adjacent to the most severely affected vessels, there is rarefaction of the neuropil (necrosis) and replacement by moderate numbers of foamy gitter cells, neutrophils and lymphocytes, fibrin, and necrotic debris. Less severely affected vessels are often lined by hypertrophied (reactive) endothelium and surrounded by increased clear space (perivascular edema).
MORPHOLOGIC DIAGNOSIS: Cerebrum, level of the hippocampus: Vasculitis, fibrinonecrotic, periventricular, choroidal, and meningeal, multifocal, severe, with moderate neutrophilic and lymphhistiocytic choriomeningoencephalitis and ventriculitis, chow chow, canine.
ETIOLOGIC DIAGNOSIS: Rickettsial vasculitis and choriomeningoencephalitis
CAUSE: Rickettsia rickettsii
CONDITION: Rocky Mountain spotted fever (RMSF), Brazilian spotted fever
· Members of order Rickettsiales are vector-borne obligate intracellular bacteria that cause (1) spotted fevers (including R. rickettsii); (2) epidemic typhus; and (3) scrub typhus
· Order Rickettsiales, family Rickettsiaceae includes genera (1) Rickettsia; (2) Ehrlichia; (3) Neorickettsia; (4) Anaplasma; (5) Cowdria; and (6) Aegyptianella
· Rickettsia rickettsii infects dogs and humans in North and South America
· Tick-borne rickettsial disease that causes vasculitis and thrombosis in many organs, especially those with abundant endarterial circulation (e.g. brain, dermis, gastrointestinal tract, heart, lung, kidneys, and skeletal muscle)
· Ticks serve as vectors, reservoirs, and natural hosts (regionally variable):
· Dermacentor variabilis (American dog tick): Eastern North America
· Dermacentor andersoni (wood tick): Western North America
· Amblyomma cajennense (Cayenne tick): Latin America
· Amblyomma americanum (Lone Star tick) and Rhipicephalus sanguineus (brown dog tick) can also serve as vectors
PATHOGENESIS: Tick-to-tick transmission is both horizontal and vertical
· Infection is usually from tick bites (can occur from contact with hemolymph or feces from infected ticks) and usually during tick season (April to September)
· Incubation period (2-14 days) > enters circulation > enters endothelial cells of small blood vessels by endocytosis > escapes endosome before formation of acidified phagolysosome > proliferates in cytoplasm > spread from cell to cell through actin-mobilized motion (spotted fever group) or lyse cell (typhus group) > endothelial swelling and necrosis (likely mediated by phospholipase A and a trypsin-like protease of either host or rickettsial origin) and platelet activation > increased vascular permeability and exposure of basement membrane > activates kallikrein-kinin system > activation of coagulation and fibrinolytic cascades > end result - tissue necrosis, thrombosis, microinfarction and hemorrhage
· Organs with endarteries (e.g. brain, dermis, gastrointestinal tract, heart, lung, kidneys, and skeletal muscle) are more severely affected
TYPICAL CLINICAL FINDINGS:
· German shepherds and Siberian huskies may be predisposed
· Fever, edema and hyperemia of the lips, prepuce, scrotum, pinna and dependent portions of the body
· Petechial and ecchymotic hemorrhages – ocular (retinal hemorrhage and uveitis are common in the dog), oral, and genital mucous membranes
· Neurologic signs - lethargy, confusion, stupor, vestibular disease, nystagmus, ataxia and circling
· Epistaxis, melena and hematuria occur in severely affected animals
· Hemorrhagic diathesis or thrombosis can result in death
· Dyspnea and coughing
· Lameness from joint or muscle pain
· Clinical pathology:
· Thrombocytopenia – consumption secondary to vasculitis; possible immune-mediated platelet destruction
· Leukopenia (initially) then progressive, moderate leukocytosis with a minimal left shift
· Mild normocytic-normochromic anemia
· Serum chemistry – hypercholesterolemia, hypoproteinemia, hypoalbuminemia, hyponatremia, hypocalcemia (often related to hypoalbuminemia), mild increase in liver enzymes
· Coagulation abnormalities – hyperfibrinogenemia, prolonged ACT or APTT; fulminant DIC is uncommon, but can occur with concurrent sepsis
TYPICAL GROSS FINDINGS:
· Edema and hyperemia: Lips, pinna, scrotum and dependent portions of the body
· Widespread petechial and ecchymotic hemorrhages in all tissues, especially caudal abdominal skin, mucous membranes, gastric wall, and pleura
· Generalized hemorrhagic lymphadenomegaly and splenomegaly
· Ulcerative glossitis, scrotal dermatitis, hemorrhagic colitis
· Retinal hemorrhage and uveitis
TYPICAL LIGHT MICROSCOPIC FINDINGS:
· Necrotizing vasculitis of small veins, capillaries, and arterioles, with perivascular lymphohistiocytic infiltrates:
· Most common in skin, testes, digestive tract, pancreas, kidneys, urinary bladder, heart, meninges, retina, and skeletal muscle
· +/- Acute meningoencephalitis, splenitis, interstitial pneumonia, myocardial necrosis, adrenal necrosis, hepatic necrosis, glomerulonephritis
· Gram negative-type three-layered cell wall with an electron lucent slime layer
ADDITIONAL DIAGNOSTIC TESTS:
· Serology: Comparison of acute and convalescent titers; species-specific microimmunofluorescent method is most reliable serologic test
· Direct fluorescent antibody staining of skin biopsy
· Organisms have the structure of gram-negative, rod-shaped bacteria, however, they stain poorly with Gram stain
· Special histologic stains - Giemsa, Gimenez, Macchiavello
· Ehrlichia canis: CNS - nonsuppurative perivascular meningitis; difficult to distinguish from RMSF due to similar signs (vasculitis); Ehrlichia has a year round occurrence and is more chronic and progressive
· Ehrlichia canis: perivascular plasmacytosis
· Neorickettsia helmintheca (salmon disease): Vasculitis not characteristic; nonsuppurative leptomeningitis in CNS
· Male guinea pig is the animal model for the disease
· Cats and other domestic animals may be seropositive without clinical disease
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